title: Lipophilic derivatives of natural chlorins: synthesis, mixed micelles with phospholipids, and uptake by cultured cells.
abstract: The chemical synthesis of six lipophilic conjugates of chlorins was carried out, in which lipophilic fragment (either hexadecyl- or cholest-5-en-3β-yloxyethyl-) bound to 13(1)-, 15(2)-, 17(3)-positions of macrocycle by formation of related carboxamides. Structure of synthesized conjugates was studied by spectral methods and molecular modeling. Lipophilic conjugates of chlorins, being mixed with egg yolk phosphatidyl choline, formed mixed micelles stable in aqueous media under physiological conditions. Mixed micelles of conjugates with phosphatidyl choline differing in stoichiometric compositions were prepared and characterized by absorption spectra, electron microscopy and laser scattering. These micelles were found to bind and internalized by human breast carcinoma MCF-7 cells. The presented data reveal that modification of macrocycle with lipophilic substituents, solubilization of obtained conjugates in aqueous medium as mixed micelles with phospholipids, and transfer of mixed micelles to cells is simple approach for targeting of chlorin derivatives, which apparently may be used in photodynamic therapy.
authors.affiliation: Orekhovich Institute of Biomedical Chemistry RAMS, 10, Pogodinskaya Street, 119121 Moscow, Russia. gelii@yandex.ru
authors.forename: Gelii V
authors.initials: GV
authors.lastname: Ponomarev
authors.forename: Maria N
authors.initials: MN
authors.lastname: Solovieva
authors.forename: Nikita O
authors.initials: NO
authors.lastname: Dugin
authors.forename: Maria G
authors.initials: MG
authors.lastname: Zavialova
authors.forename: Arif R
authors.initials: AR
authors.lastname: Mehtiev
authors.forename: Alexander Yu
authors.initials: AY
authors.lastname: Misharin
authors.forename: Roman A
authors.initials: RA
authors.lastname: Novikov
authors.forename: Yaroslav V
authors.initials: YV
authors.lastname: Tkachev
authors.forename: Vladimir I
authors.initials: VI
authors.lastname: Popenko
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Timofeev
mesh_terms: D006801:Humans; D061986:MCF-7 Cells; D008823:Micelles; D008956:Models, Chemical; D010713:Phosphatidylcholines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D011166:Porphyrins / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D014867:Water / Q000737:chemistry
chemical_list: D008823:Micelles; D010713:Phosphatidylcholines; D010743:Phospholipids; D011166:Porphyrins; D014867:Water; C006969:chlorin
keywords: Drug delivery; Lipophilic chlorin derivatives; Mixed micelles; Synthesis